Chronic PainNCT05427201
Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy
A study testing Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy in people with Chronic Pain and Depression, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Pain, Depression
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 22 May 2023to 30 May 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of a chronic, non-terminal pain condition (pain most days for at least 6 months)
- Average pain intensity and interference with enjoyment of life and/or general activity rated > 4/10 over the past week, as measured by the PEG
- Meet clinical criteria for major depression via DSM5 criteria, as assessed by the Mini International Neuropsychiatric Interview (MINI)
Who cannot join
- Serious or unstable medical illness (e.g., cardiovascular disease)
- Lifetime history of psychotic disorder, bipolar disorder, obsessive-compulsive disorder
- Active substance abuse or psychosocial instability (e.g., homelessness) that could compromise study participation
- Changes to professionally delivered pain or mood treatment (e.g., no discontinuation of a treatment; no increasing the dose of medication) one month preceding the baseline assessment
- Significant neurologic disorder, increased risk of seizure for any reason or family/personal history of seizure
- Contraindications to rTMS treatment as outlined by the Safety of TMS Consensus group, which includes implanted metallic objects above the neck, implanted electrical devices (pacemakers/spinal cord stimulators), and pregnancy
- Prior trial of rTMS for any condition and/or lack of responsiveness to electroconvulsive therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
About this study
Official title: Integrated Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy for Veterans With Chronic Pain and Depression
Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. The investigators will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.
Read the detailed description
Comorbid depression is highly prevalent in Veterans with chronic pain and contributes to greater pain severity, functional impairment, and suicide risk relative to those with chronic pain alone. Despite the well-known association between chronic pain and depression, current treatments fall short of producing meaningful improvements in function and quality of life in this population. In this application, the investigators propose to address this problem by a novel intervention that combines repetitive Transcranial Magnetic Stimulation (rTMS) and Acceptance and Commitment Therapy (ACT).
ACT is an evidence-based psychosocial intervention that improves function in Veterans with chronic pain. However, similar to the broader literature, comorbid depression significantly limits the efficacy of ACT, which may be directly related to dysfunctional brain circuits that maintain depression. rTMS is a non-invasive brain stimulation intervention that is FDA-cleared for the treatment of depression. The most commonly targeted stimulation area is the left dorsolateral prefrontal cortex (DLFPC), a prefrontal brain region involved in cognitive control and emotion regulation. rTMS over the left DLPFC has also been used to reduce pain intensity in patients with chronic pain, as the DLPFC is implicated in the affective processing of painful stimuli. Importantly, while rTMS has been shown to reduce depression severity and pain intensity, it does not directly address function. Thus, the proposed research will integrate rTMS and ACT with the goal of maximizing functional improvement in Veterans with chronic pain and depression.
The purpose of this application is to examine the feasibility of a future randomized efficacy trial. A total of 24 Veterans with chronic pain and depression will be randomized into DLPFC-rTMS + ACT or sham-rTMS + ACT conditions. Multiple metrics of feasibility will be assessed, including general interest in the study, willingness to participate, enrollment, retention, drop-out, number of adverse events, and participant blindness to condition, as well as ratings of credibility, expectation, and treatment satisfaction. The investigators will also estimate the preliminary impact of DLPFC-rTMS + ACT and sham-rTMS + ACT on function as measured by reductions in pain interference (primary clinical outcome). The intent of preliminary analyses is to obtain an additional indicator for a future large-scale trial, not to verify group differences. Further, the investigators will include two cognitive control tasks, the Emotion Distractor and Attention-to-Breath tasks, with concurrent EEG recording as a potential objective indicator of treatment response. The study team has previously demonstrated the association between depression severity and DLPFC activity on these tasks. In the proposed study, the investigators will explore the associations between treatment-related change in DLPFC activity and treatment outcomes.
Veterans with chronic pain and depression do not have access to effective treatments. To address this need, the investigators seek to examine the feasibility of a novel approach by integrating a somatic and a psychosocial intervention. The investigator's scientific premise is that rTMS over the left DLPFC will remediate hypofunction of prefrontal brain circuits that is necessary to maximize the impact of ACT on function in Veterans with chronic pain and depression. Findings from the proposed research have the potential of substantially increasing the physical and psychosocial functioning of Veterans with chronic pain and depression.
- Conditions
- Chronic Pain, Depression
- Being tested
- Repetitive Transcranial Magnetic Stimulation, Acceptance and Commitment Therapy
- Keywords
- Chronic pain, Depression, Repetitive transcranial magnetic stimulation, Acceptance and commitment therapy
- Medical subject headings
- Chronic Pain, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
Also called rTMS
rTMS is a non-invasive brain stimulation technique designed to alter network function
Acceptance and Commitment TherapyBehavioural
Also called ACT
ACT is a mindfulness-based cognitive behavioral intervention that has demonstrated efficacy for chronic pain.
| Study group | Role | What they receive |
|---|---|---|
| DLPFC-rTMS + ACT | Experimental | Active DLPFC-rTMS with ACT treatment Receives: Device: Repetitive Transcranial Magnetic Stimulation; Behavioral: Acceptance and Commitment Therapy |
| Sham-rTMS + ACT | Active comparator | Sham delivered rTMS with ACT treatment Receives: Behavioral: Acceptance and Commitment Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
PROMIS Pain Interference Change
The PROMIS Pain Interference questionnaire consists of 8-items that assess the degree to which pain interferes with various aspects of life, including mobility, social activity, and mood. Items are scored on a 1 ("Not at all") to 5 ("Very much") scale with a range of 8 - 40. These scores are subsequently transcribed to a T-score. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain interference. A 10-point difference represents one standard deviation from the reference population mean.
Measured: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
Secondary outcomes (2)
Patient Health Questionnaire-9 Change
The PHQ-9 is a widely used measure of depressive symptoms. Items are scored on a 0 ("not at all") to 3 ("Nearly every day") scale with a range of 0 - 27. Higher scores indicate greater depression severity.
Measured: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
PROMIS Pain Intensity Change
The PROMIS Pain Intensity questionnaire consists of 3 items assessing worst and average pain over the past week, as well as current pain. Items are scored on a 1 ("No pain") to 5 ("Very severe") scale with a range of 3 - 15. Total scores are subsequently converted to T-scores. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain intensity. A 10-point difference represents one standard deviation from the reference population mean.
Measured: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2022
- Study start22 May 2023
- Primary completion30 May 2025
- Study completion30 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controlled Trial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Matthew Herbert, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05427201
- Sponsor's protocol ID
- D4090-P
- Other IDs
- RX004090
- Status last verified
- Jul 2026
- First submitted
- 15 Jun 2022
- Last updated
- 17 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: A data repository will be created upon completion of the study. Data obtained in this study that has scientific value to other qualified researchers will made available upon request. Interested researches will be able to access de-identified data through a Data Use Agreement.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrated Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy for Veterans With Chronic Pain and Depression
- ClinicalTrials.gov ID
- NCT05427201
- Acronym / sponsor ID
- D4090-P
- Conditions
- Chronic Pain, Depression
- Keywords
- Chronic pain, Depression, Repetitive transcranial magnetic stimulation, Acceptance and commitment therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 22 May 2023 (actual)
- Primary completion
- 30 May 2025 (actual)
- Study completion
- 30 May 2025 (actual)
- First posted
- 22 Jun 2022 (actual)
- Results
- Posted 17 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. The investigators will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.
Detailed description
Comorbid depression is highly prevalent in Veterans with chronic pain and contributes to greater pain severity, functional impairment, and suicide risk relative to those with chronic pain alone. Despite the well-known association between chronic pain and depression, current treatments fall short of producing meaningful improvements in function and quality of life in this population. In this application, the investigators propose to address this problem by a novel intervention that combines repetitive Transcranial Magnetic Stimulation (rTMS) and Acceptance and Commitment Therapy (ACT).
ACT is an evidence-based psychosocial intervention that improves function in Veterans with chronic pain. However, similar to the broader literature, comorbid depression significantly limits the efficacy of ACT, which may be directly related to dysfunctional brain circuits that maintain depression. rTMS is a non-invasive brain stimulation intervention that is FDA-cleared for the treatment of depression. The most commonly targeted stimulation area is the left dorsolateral prefrontal cortex (DLFPC), a prefrontal brain region involved in cognitive control and emotion regulation. rTMS over the left DLPFC has also been used to reduce pain intensity in patients with chronic pain, as the DLPFC is implicated in the affective processing of painful stimuli. Importantly, while rTMS has been shown to reduce depression severity and pain intensity, it does not directly address function. Thus, the proposed research will integrate rTMS and ACT with the goal of maximizing functional improvement in Veterans with chronic pain and depression.
The purpose of this application is to examine the feasibility of a future randomized efficacy trial. A total of 24 Veterans with chronic pain and depression will be randomized into DLPFC-rTMS + ACT or sham-rTMS + ACT conditions. Multiple metrics of feasibility will be assessed, including general interest in the study, willingness to participate, enrollment, retention, drop-out, number of adverse events, and participant blindness to condition, as well as ratings of credibility, expectation, and treatment satisfaction. The investigators will also estimate the preliminary impact of DLPFC-rTMS + ACT and sham-rTMS + ACT on function as measured by reductions in pain interference (primary clinical outcome). The intent of preliminary analyses is to obtain an additional indicator for a future large-scale trial, not to verify group differences. Further, the investigators will include two cognitive control tasks, the Emotion Distractor and Attention-to-Breath tasks, with concurrent EEG recording as a potential objective indicator of treatment response. The study team has previously demonstrated the association between depression severity and DLPFC activity on these tasks. In the proposed study, the investigators will explore the associations between treatment-related change in DLPFC activity and treatment outcomes.
Veterans with chronic pain and depression do not have access to effective treatments. To address this need, the investigators seek to examine the feasibility of a novel approach by integrating a somatic and a psychosocial intervention. The investigator's scientific premise is that rTMS over the left DLPFC will remediate hypofunction of prefrontal brain circuits that is necessary to maximize the impact of ACT on function in Veterans with chronic pain and depression. Findings from the proposed research have the potential of substantially increasing the physical and psychosocial functioning of Veterans with chronic pain and depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| DLPFC-rTMS + ACT | Experimental | Device: Repetitive Transcranial Magnetic Stimulation, Behavioral: Acceptance and Commitment TherapyActive DLPFC-rTMS with ACT treatment |
| Sham-rTMS + ACT | Active comparator | Behavioral: Acceptance and Commitment TherapySham delivered rTMS with ACT treatment |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of a chronic, non-terminal pain condition (pain most days for at least 6 months)
- Average pain intensity and interference with enjoyment of life and/or general activity rated > 4/10 over the past week, as measured by the PEG
- Meet clinical criteria for major depression via DSM5 criteria, as assessed by the Mini International Neuropsychiatric Interview (MINI)
Key exclusion criteria (7 listed)
- Serious or unstable medical illness (e.g., cardiovascular disease)
- Lifetime history of psychotic disorder, bipolar disorder, obsessive-compulsive disorder
- Active substance abuse or psychosocial instability (e.g., homelessness) that could compromise study participation
- Changes to professionally delivered pain or mood treatment (e.g., no discontinuation of a treatment; no increasing the dose of medication) one month preceding the baseline assessment
- Significant neurologic disorder, increased risk of seizure for any reason or family/personal history of seizure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationAlso: rTMSrTMS is a non-invasive brain stimulation technique designed to alter network function | Device | DLPFC-rTMS + ACT |
| Acceptance and Commitment TherapyAlso: ACTACT is a mindfulness-based cognitive behavioral intervention that has demonstrated efficacy for chronic pain. | Behavioural | DLPFC-rTMS + ACT, Sham-rTMS + ACT |
Primary outcome
PROMIS Pain Interference Change
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
The PROMIS Pain Interference questionnaire consists of 8-items that assess the degree to which pain interferes with various aspects of life, including mobility, social activity, and mood. Items are scored on a 1 ("Not at all") to 5 ("Very much") scale with a range of 8 - 40. These scores are subsequently transcribed to a T-score. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain interference. A 10-point difference represents one standard deviation from the reference population mean.
2 secondary outcomes
Patient Health Questionnaire-9 Change
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
PROMIS Pain Intensity Change
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. A data repository will be created upon completion of the study. Data obtained in this study that has scientific value to other qualified researchers will made available upon request. Interested researches will be able to access de-identified data through a Data Use Agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Herbert, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy in people with Chronic Pain and Depression, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PROMIS Pain Interference Change (time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.